Treponema pallidum is the etiologic agent of syphilis, a multistage sexually transmitted disease that is a global health problem. Identification of virulence determinants and protective immunogens of T. pallidum has been hindered by the non-cultivable nature of this spirochete. Although T. pallidum has a cellular architecture similar to Gram negative bacteria, its outer membrane contains rare, poorly immunogenic proteins whose identified and functions remain elusive. Using TnphoA mutagenesis, we identified a gene (tprJ) encoding a protein with homology to the major surface protein of T. denticola, a periodontal pathogen. The tprJ is a member of a polymorphic multi-gene family encoding 12 proteins (TprA- L), that are divided into three subgroups. Recent studies have shown heterogeneity in the subgroup 3 (tprJ, tprE, and tprG) genes. We hypothesize that functional activities such as attachment, invasion, etc. The long-term goal of our studies is to develop a better understanding of variation of the subgroup 3 tpr genes and their corresponding proteins. The specific aims for the project are: (1) To detect nucleotide sequence variations within or flanking the tprJ, tprE, and tprG genes of T. pallidum obtained a various timepoints from chances of intradermally infected rabbits; (2) To examine expression of the TprJ, TprE and TprG proteins in T. pallidum and to assess the kinetics of the rabbit IgG antibodies to the TprJ, TprE and TprG proteins and to peptides representing the variable and/or conserved regions of the Tpr proteins; (4) To determine if immunization of rabbits with the TprJ, TprE, and TprG proteins of peptide protects against infection with T. pallidum and/or selects for phenotypic variants and (5) To evaluate nucleotide sequence variability of the tprJ, tprE, and tprG genes of T. pallidum in clinical specimens from syphilis patients attending local STD clinics.